We previously had shown that the proto-dbl product contains a region with significant sequence similarity to a Saccharomyces cerevisiae cell cycle gene product, CDC24. CDC24 is known to be involved in the establishment of cell polarity and bud formation and to participate in the same signalling pathway as CDC42, another yeast cell-division cycle protein which belongs to the superfamily of low molecular mass GTP proteins. We have shown that the dbl oncogene product, expressed in insect cells, specifically catalyses the dissociation of GDP from the human homolog of yeast CDC42, CDC42HS, and thus qualifies as a highly selective guanine nucleotide exchange factor for the GTP-binding protein. We investigated the expression of the dbl proto-oncogene in a wide variety of human tumors of different embryological derivation. We found that proto-dbl mRNA could be detected preferentially in a few neoplastic histiotypes of neuroectodermal origin. While our results indicate that proto-dbl in these tumors was not rearranged, they suggest that the dbl proto-oncogene is expressed in a highly tissue-specific manner and indicate that this gene may be involved in the growth and differentiation of some cells of neuroectodermal origin.